Targeting tumor-associated macrophages (TAMs) holds great promise for cancer immunotherapy. Surface glycoproteins in macrophages regulate their interactions with tumor cells and represent emerging therapeutic targets. Given the crucial roles of protein glycosylation in immune function and cancer, we systematically investigate the total and surface glycoproteomes in polarized macrophages using multiplexed proteomics coupled with selective enrichment. Using THP-1 monocyte-derived macrophages, we uncovered distinct N-glycosylation patterns between M1 and M2 phenotypes, with differential regulation primarily driven by changes in protein expression and nucleotide sugar biosynthesis. Furthermore, we performed systematic analysis of surface glycoproteins in primary human macrophages with M1 or M2 phenotype (HM1 and HM2), and the results revealed extensive, phenotype-specific remodeling of the cell-surface glycoproteome: HM1 macrophages displayed enhanced innate immune signaling, whereas in HM2 macrophages, surface glycoproteins related to adhesion, endocytosis, and angiogenesis were upregulated. Comparative analysis between THP-1-derived and primary human macrophages highlights both shared and divergent features of surface remodeling, emphasizing the value of primary cell systems for physiological relevance. Integrative analyses combining cell-surface glycoproteomic, transcriptomic, and tissue-specific datasets identified surface proteins as potential targets for inhibiting M2 macrophages, including some previously underexplored ones (such as LIPA, CD200R1, and CR1). Together, this study provides a comprehensive macrophage glycoproteome atlas and establishes a framework for developing TAM-directed cancer immunotherapies.